TY - JOUR
T1 - Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation
AU - Hoxworth, Joseph M.
AU - Xu, Kui
AU - Zhou, Yinong
AU - Lust, W. David
AU - Lamanna, Joseph C.
N1 - Funding Information:
This study was supported by PHS Grants NS22077 and NS37111. JMH was supported in part by a Student Scholarship in Cerebrovascular Disease from the American Heart Association Stroke Council. We wish to express our most sincere thanks to Suzanne Foss and Kimberly Nelson who made our work possible through their administrative and technical support.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/3/13
Y1 - 1999/3/13
N2 - Cortical metabolites and regional cerebral intracellular pH (pH(i)) were measured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2 week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest and resuscitation. During total ischemia in AH and CH rats (plasma glucose ~ 30 mM), cortical ATP, PCr, glucose, and glycogen all fell significantly as expected. Lactate levels increased dramatically in association with a concomitant intracellular acidosis. Although lactate reached higher concentrations in AH and CH than NM, pH(i) was significantly lower only in the AH group. With 5 min of reperfusion, all groups recovered to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group were allowed to recover for 4 days following resuscitation, with outcome being gauged by mortality rate and hippocampal CA1 neuron counts. NM survival rate was significantly better than AH and CH. In particular, no CH rats survived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In summary, our research identified differences in intra-ischemic acid-base status in the two hyperglycemic groups, suggesting that chronic hyperglycemia may alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regarding outcome, and they suggest that factors other than hydrogen ion production during ischemia are responsible for modulating outcome.
AB - Cortical metabolites and regional cerebral intracellular pH (pH(i)) were measured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2 week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest and resuscitation. During total ischemia in AH and CH rats (plasma glucose ~ 30 mM), cortical ATP, PCr, glucose, and glycogen all fell significantly as expected. Lactate levels increased dramatically in association with a concomitant intracellular acidosis. Although lactate reached higher concentrations in AH and CH than NM, pH(i) was significantly lower only in the AH group. With 5 min of reperfusion, all groups recovered to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group were allowed to recover for 4 days following resuscitation, with outcome being gauged by mortality rate and hippocampal CA1 neuron counts. NM survival rate was significantly better than AH and CH. In particular, no CH rats survived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In summary, our research identified differences in intra-ischemic acid-base status in the two hyperglycemic groups, suggesting that chronic hyperglycemia may alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regarding outcome, and they suggest that factors other than hydrogen ion production during ischemia are responsible for modulating outcome.
KW - Global complete cerebral ischemia
KW - High-energy phosphate
KW - Intracellular pH
KW - Lactic acidosis
KW - Selective neuronal vulnerability
KW - Streptozotocin-induced diabetes
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U2 - 10.1016/S0006-8993(98)01332-8
DO - 10.1016/S0006-8993(98)01332-8
M3 - Article
C2 - 10064834
AN - SCOPUS:0033550933
SN - 0006-8993
VL - 821
SP - 467
EP - 479
JO - Brain Research
JF - Brain Research
IS - 2
ER -